Climate Change Promotes the Emergence of Serious Disease Outbreaks of Filarioid Nematodes

Filarioid parasites represent major health hazards with important medical, veterinary, and economic implications, and considerable potential to affect the everyday lives of tens of millions of people globally (World Health Organization, 2007). Scenarios for climate change vary latitudinally and regionally and involve direct and indirect linkages for increasing temperature and the dissemination, amplification, and invasiveness of vector-borne parasites. High latitude regions are especially influenced by global climate change and thus may be prone to altered associations and dynamics for complex host-pathogen assemblages and emergence of disease with cascading effects on ecosystem structure. Although the potential for substantial ecological perturbation has been identified, few empirical observations have emanated from systems across the Holarctic. Coincidental with decades of warming, and anomalies of high temperature and humidity in the sub-Arctic region of Fennoscandia, the mosquito-borne filarioid nematode Setaria tundra is now associated with emerging epidemic disease resulting in substantial morbidity and mortality for reindeer and moose. We describe a host-parasite system that involves reindeer, arthropods, and nematodes, which may contribute as a factor to ongoing declines documented for this ungulate species across northern ecosystems. We demonstrate that mean summer temperatures exceeding 14°C drive the emergence of disease due to S. tundra. An association between climate and emergence of filarioid parasites is a challenge to ecosystem services with direct effects on public health, sustainability of free-ranging and domestic ungulates, and ultimately food security for subsistence cultures at high latitudes.     

Variable responses of waterfowl breeding populations to long-term removal of introduced American mink

It is suspected that feral American mink, an introduced predator in Europe, have seriously affected local densities of birds breeding in archipelagos and coastal areas. We studied the effects of mink removal on breeding densities of waterfowl in two manipulation and two control areas in the outer archipelago of SW Finland, Baltic Sea. The study was conducted in two phases: during 1992–2001 a total of 98 mink was removed from 60 islands and islets (total area 72 km²) whereas on 37 islands and islets (35 km²) mink was not removed. Additional mink removal and control areas were established during 1998–2001 to replicate the experiment. The breeding densities of the shelduck, tufted duck and the velvet scoter increased as a response to mink removal, while in the control areas their populations remained unchanged. The breeding densities of mallards increased during the first 7 yr of mink removal, but a steep decrease in the last study year resulted in a statistically non-significant overall increase. The species with low breeding densities (the gadwall, northern shoveler, pintail and the red-breasted merganser) increased as well. In contrast, the populations of large waterfowl species, the mute swan, greylag goose, common eider and the goosander, did not show obvious increases in breeding densities after mink removal. We conclude that feral mink may locally limit the breeding densities of some smaller waterfowl species and thus reduce the diversity of the waterfowl community in the outer archipelago.     

Impacts of climate warming on the long-term dynamics of key fish species in 24 European lakes

Fish play a key role in the trophic dynamics of lakes. With climate warming, complex changes in fish assemblage structure may be expected owing to direct effects of temperature and indirect effects operating through eutrophication, water level changes, stratification and salinisation. We reviewed published and new long-term (10–100 years) fish data series from 24 European lakes (area: 0.04–5,648 km²; mean depth: 1–177 m; a north–south gradient from Sweden to Spain). Along with an annual temperature increase of about 0.15–0.3°C per decade profound changes have occurred in either fish assemblage composition, body size and/or age structure during recent decades and a shift towards higher dominance of eurythermal species. These shifts have occurred despite a reduction in nutrient loading in many of the lakes that should have benefited the larger-sized individuals and the fish species typically inhabiting cold-water, low-nutrient lakes. The cold-stenothermic Arctic charr has been particularly affected and its abundance has decreased in the majority of the lakes where its presence was recorded. The harvest of cool-stenothermal brown trout has decreased substantially in two southern lakes. Vendace, whitefish and smelt show a different response depending on lake depth and latitude. Perch has apparently been stimulated in the north, with stronger year classes in warm years, but its abundance has declined in the southern Lake Maggiore, Italy. Where introduced, roach seems to take advantage of the higher temperature after years of low population densities. Eurythermal species such as common bream, pike–perch and/or shad are apparently on the increase in several of the lakes. The response of fish to the warming has been surprisingly strong and fast in recent decades, making them ideal sentinels for detecting and documenting climate-induced modifications of freshwater ecosystems.     

Effects of novel C-methylated spermidine analogs on cell growth via hypusination of eukaryotic translation initiation factor 5A

The polyamines, putrescine, spermidine, and spermine, are ubiquitous multifunctional cations essential for cellular proliferation. One specific function of spermidine in cell growth is its role as a butylamine donor for hypusine synthesis in the eukaryotic initiation factor 5A (eIF5A). Here, we report the ability of novel mono-methylated spermidine analogs (α-MeSpd, β-MeSpd, γ-MeSpd, and ω-MeSpd) to function in the hypusination of eIF5A and in supporting the growth of DFMO-treated DU145 cells. We also tested them as substrates and inhibitors for deoxyhypusine synthase (DHS) in vitro. Of these compounds, α-MeSpd, β-MeSpd, and γ-MeSpd (but not ω-MeSpd) were substrates for DHS in vitro, while they all inhibited the enzyme reaction. As racemic mixtures, only α-MeSpd and β-MeSpd supported long-term growth (9-18 days) of spermidine-depleted DU145 cells, whereas γ-MeSpd and ω-MeSpd did not. The S-enantiomer of α-MeSpd, which supported long-term growth, was a good substrate for DHS in vitro, whereas the R-isomer was not. The long-term growth of DFMO-treated cells correlated with the hypusine modification of eIF5A by intracellular methylated spermidine analogs. These results underscore the critical requirement for hypusine modification in mammalian cell proliferation and provide new insights into the specificity of the deoxyhypusine synthase reaction.     

Tissue-specific alternative splicing of spermidine/spermine N 1-acetyltransferase

The polyamines, spermidine and spermine, are abundant organic cations participating in many important cellular processes. We have previously shown that the rate-limiting enzyme of polyamine catabolism, spermidine/spermine N ¹-acetyltransferase (SSAT), has an alternative mRNA splice variant (SSATX) which undergoes degradation via nonsense-mediated mRNA decay (NMD) pathway, and that the intracellular polyamine level regulates the ratio of the SSATX and SSAT splice variants. The aim of this study was to investigate the effect of SSATX level manipulation on SSAT activity in cell culture, and to examine the in vivo expression levels of SSATX and SSAT mRNA. Silencing SSATX expression with small interfering RNA led to increased SSAT activity. Furthermore, transfection of SSAT-deficient cells with mutated SSAT gene (which produced only trace amount of SSATX) yielded higher SSAT activity than transfection with natural SSAT gene (which produced both SSAT and SSATX). Blocking NMD in vivo by protein synthesis inhibitor cycloheximide resulted in accumulation of SSATX mRNA, and like in cell culture, the increase of SSATX mRNA was prevented by administration of polyamine analog N ¹ ,N ¹¹ -diethylnorspermine. Although SSATX/total SSAT mRNA ratio did not correlate with polyamine levels or SSAT activity between different tissues, increasing polyamine levels in a given tissue led to decreased SSATX/total SSAT mRNA ratio and vice versa. Taken together, the regulated unproductive splicing and translation of SSAT has a physiological relevance in modulating SSAT activity. However, in addition to polyamine level there seems to be additional factors regulating tissue-specific alternative splicing of SSAT.     

Inducible expression of antizyme 1 in prostate cancer cell lines after lentivirus mediated gene transfer

The prostate has the highest level of polyamines among all tissues, and it is the only tissue in which polyamines are purposely synthesized for export. It has been suggested that the high local polyamine concentrations suppress cell growth of primary prostatic carcinomas and that this growth control is lost when cancer cells metastasize. It has also been shown that the sensitivity to polyamine-induced growth arrest correlates with antizyme induction in prostate carcinoma cell lines. In this study, we evaluated the sensitivity of poorly metastatic (LNCaP) and highly metastatic (DU145) prostate cancer cell lines to conditional antizyme 1 over-expression. Antizyme 1 induction resulted in a marked loss of ODC activity and polyamine uptake in both cell lines. However, the proliferation of LNCaP cells was repressed by antizyme 1 induction, whereas the proliferation of DU 145 cells was not affected. Neither cell line showed any reduction in polyamine pools after manipulation nor did polyamine addition into the medium save the LNCaP cells from the growth retardation. The growth inhibition of LNCaP cells was accompanied by accumulation of cells in the G1 phase and depletion of cyclin E1 protein. These results confirm that different prostate cancer cell lines show diverse sensitivities to antizyme 1 which may not be directly polyamine related. The high gene transfer capacity of the used lentiviral vector makes the present approach a useful tool to study the therapeutic potential of antizyme 1 both in cell cultures and experimental animals.     

Night work and mortality: prospective study among Finnish employees over the time span 1984 to 2008

There is considerable evidence showing that night work is associated with increased morbidity, but only a few studies have focused on its relation to mortality. This study investigates the relationship between the type of working-time arrangement (weekly night work/daytime work) and total and cause-specific mortality among men and women. The data consist of a representative working conditions survey of Finnish employees conducted in 1984 (2286 men/2216 women), which has been combined with register-based follow-up data from Statistics Finland covering the years 1985-2008. In the 1984 survey, the employees were asked if they worked during the night (23:00-06:00 h) and if so, how often. In this study, the authors compare employees who worked at night (121 men/89 women) to daytime employees who did not do night work (1325 men/1560 women). The relative risk of death was examined by Cox proportional hazards analyses adjusted for background (age, level of education, family situation, and county), health (longstanding illness, pain symptoms, smoking status, and psychological symptoms), and work-related factors (weekly working hours, physical and psychological demands, demands of learning at work, and perceived job insecurity). Female employees working at night had a 2.25-fold higher risk of mortality than female dayworkers (95% confidence interval [CI] 1.20-4.20) after adjustment for background and health- and work-related factors. In addition to total mortality, night work was also associated with tumor mortality. Female night workers had a 2.82-fold higher risk of tumor mortality than female dayworkers (95% CI 1.20-6.65) in the adjusted model. Among men, no such significant association was observed. The present study indicated that female night workers had a higher risk of both total and tumor mortality compared to female daytime employees. Additional research on the potential factors and mechanisms behind the association between night work and mortality is required.     

Two-Stage Processing of Sounds Explains Behavioral Performance Variations due to Changes in Stimulus Contrast and Selective Attention: An MEG Study

Selectively attending to task-relevant sounds whilst ignoring background noise is one of the most amazing feats performed by the human brain. Here, we studied the underlying neural mechanisms by recording magnetoencephalographic (MEG) responses of 14 healthy human subjects while they performed a near-threshold auditory discrimination task vs. a visual control task of similar difficulty. The auditory stimuli consisted of notch-filtered continuous noise masker sounds, and of 1020-Hz target tones occasionally () replacing 1000-Hz standard tones of 300-ms duration that were embedded at the center of the notches, the widths of which were parametrically varied. As a control for masker effects, tone-evoked responses were additionally recorded without masker sound. Selective attention to tones significantly increased the amplitude of the onset M100 response at 100 ms to the standard tones during presence of the masker sounds especially with notches narrower than the critical band. Further, attention modulated sustained response most clearly at 300–400 ms time range from sound onset, with narrower notches than in case of the M100, thus selectively reducing the masker-induced suppression of the tone-evoked response. Our results show evidence of a multiple-stage filtering mechanism of sensory input in the human auditory cortex: 1) one at early (100 ms) latencies bilaterally in posterior parts of the secondary auditory areas, and 2) adaptive filtering of attended sounds from task-irrelevant background masker at longer latency (300 ms) in more medial auditory cortical regions, predominantly in the left hemisphere, enhancing processing of near-threshold sounds.     

Early environment and neurobehavioral development predict adult temperament clusters

Background

Investigation of the environmental influences on human behavioral phenotypes is important for our understanding of the causation of psychiatric disorders. However, there are complexities associated with the assessment of environmental influences on behavior.

Methods/Principal Findings

We conducted a series of analyses using a prospective, longitudinal study of a nationally representative birth cohort from Finland (the Northern Finland 1966 Birth Cohort). Participants included a total of 3,761 male and female cohort members who were living in Finland at the age of 16 years and who had complete temperament scores. Our initial analyses (Wessman et al., in press) provide evidence in support of four stable and robust temperament clusters. Using these temperament clusters, as well as independent temperament dimensions for comparison, we conducted a data-driven analysis to assess the influence of a broad set of life course measures, assessed pre-natally, in infancy, and during adolescence, on adult temperament.

Results

Measures of early environment, neurobehavioral development, and adolescent behavior significantly predict adult temperament, classified by both cluster membership and temperament dimensions. Specifically, our results suggest that a relatively consistent set of life course measures are associated with adult temperament profiles, including maternal education, characteristics of the family’s location and residence, adolescent academic performance, and adolescent smoking.

Conclusions

Our finding that a consistent set of life course measures predict temperament clusters indicate that these clusters represent distinct developmental temperament trajectories and that information about a subset of life course measures has implications for adult health outcomes.     

No association of COMT (Val158Met) genotype with brain structure differences between men and women

We examined the effect of the catechol-O-methyltransferase (COMT) Val158Met polymorphism (rs4680), on brain structure in a subset (N = 82) of general population members of the Northern Finland 1966 Birth Cohort, selected through a randomization procedure, aged 33-35. Optimised voxel-based morphometry was used to produce grey matter maps from each subject's high resolution T1 weighted brain magnetic resonance images, which were subsequently entered into a general linear model with COMT genotype as defined by Met allele loading, gender and genotype by gender interaction as independent variables. Additional analyses were carried out on grey matter volumes within the dorsal lateral pre-frontal cortex (DLPFC) to examine effects on overall DLPFC volume and also using the DLPFC as a mask for voxelwise analyses, as this is an area previously reported as associated with Met allele loading. We failed to find any statistically significant association with grey matter volume and Met allele loading in the COMT gene or interaction affects between COMT and gender in either the whole brain voxel-wise analysis or in the area of the DLPFC.